Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, Hebei, China.
Department of Epidemiology and Health Statistics, School of Life Sciences, North China University of Science and Technology, Hebei, China.
Int J Biol Macromol. 2021 Mar 1;172:321-329. doi: 10.1016/j.ijbiomac.2021.01.071. Epub 2021 Jan 15.
Previous studies by our group have demonstrated that the calcium imbalance in rat hepatic stellate cells (HSCs) can induce endoplasmic reticulum stress (ERS) and promote cell apoptosis. KN-62, an inhibitor of Calmodulin kinase II (CaMK II), can decrease the expression of CaMK II that plays a major role in regulating the steady state of intracellular Ca2+. Uridine triphosphate (UTP) plays a biological role in increasing indirectly the level of intracellular Ca2+. In the experiment, we demonstrate that KN-62 and UTP can inhibit the proliferation and promote the apoptosis in HSCs, increase the level of intracellular Ca2+ and the expression of ERS protein GRP78, and increase the apoptosis protein Caspase-12 and Bax expression, while decrease the expression of Bcl-2 protein. Our findings indicate that the CaMK II/Ca2+ signaling pathway regulates the ERS apoptosis pathway and induces HSC apoptosis.
先前本课题组的研究已经证实，大鼠肝星状细胞（HSCs）内的钙离子失衡会导致内质网应激（ERS），并促进细胞凋亡。钙调蛋白激酶 II（CaMK II）抑制剂 KN-62 可以降低在调节细胞内 Ca2+稳态中起主要作用的 CaMK II 的表达。三磷酸尿苷（UTP）在增加细胞内 Ca2+间接水平方面发挥着生物学作用。在实验中，我们证明 KN-62 和 UTP 可以抑制 HSCs 的增殖并促进其凋亡，增加细胞内 Ca2+水平和 ERS 蛋白 GRP78 的表达，并增加凋亡蛋白 Caspase-12 和 Bax 的表达，同时降低 Bcl-2 蛋白的表达。我们的研究结果表明，CaMK II/Ca2+信号通路调节 ERS 凋亡通路并诱导 HSC 凋亡。
